The present invention relates to 4-aminopyridine derivatives. The compounds of the present invention inhibit brain acetylcholinesterase and are useful in the treatment of Alzheimer's disease.
Tetrahydroaminoacridine, which has anticholinesterase activity, has been reported to produce improved performance in psychological tests in patients afflicted with Alzheimer's disease (W. K. Summers et al., The New England Journal of Medicine, 315, 1241-1245 (1986)). The anticholinesterase physostigmine has also been reportedly used in the experimental treatment of Alzheimer's disease (S. D. Brinkman et al., Neurobiol. Aging, 4, 139-145 (1983)).
The compounds described in the following four documents are alleged to have anticholinesterase activity:
U.S. Pat. No. 4,652,567 refers to benzo(C)-1,5-naphthyridines for treating Alzheimer's disease.
U.S. Pat. No. 4,631,286 refers to 9-amino-1,2,3,4-tetrahydroacridine-1-ol and related compounds for treating Alzheimer's disease.
U.S. Pat. No. 4,550,113 refers to 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)quinoline monohydrate hydrochloride for treating neuritis, injuries of the peripheral nervous system, hereditary neuromuscular diseases, and disseminated sclerosis.
U.S. Pat. No. 4,578,394 refers to dihydropyridines for treating Alzheimer's disease.
U.S. Pat. No. 4,540,564 refers to dihydropyridines for delivering drugs to the brain.
G. K. Patnaik et al., J. Med. Chem., 9, 483-488 (1966), refer to 4-substituted 2,3-polymethylenequinolines having analgetic, local anesthetic, analeptic, and respiratory stimulant activities.
British Patent Specifications 1,186,061, 1,186,062, and 1,186,063 refer to benzonaphthyridine derivatives.